SCID (severe combined immunodeficiency) presents one of the greatest opportunities for newborn screening (NBS), and also one of its most difficult challenges. This is the first condition detectable by NBS for which a cure is available, when identified and treated in early infancy (Railey et al., J Peds 2009; 155(6):834-40). However, the only test currently available with the potential of detecting SCID in the Guthrie specimen is the TREC (T-cell recombinant excision circle) assay (Chan & Puck, J Allergy Clin Immunol 2005; 115:391-8). The TREC assay presents technical challenges in that it is a primary screening assay using DNA, a protocol not accepted universally by the screening community (Green & Pass, Nat Rev Genet 2005; 6:147-55). Alternatively, immunoassays are used routinely in NBS as a first-tier screening protocol (Moyer et al., Hastings Cent Rep 2008; 38(3):32-39).
SCID (severe combined immunodeficiency) fulfills the requirements for a newborn screening (NBS) condition: sufficient prevalence (estimated at 1:50000 to 1:100000); biomarkers in the Guthrie specimen; and the availability of an appropriate therapy (bone marrow transplant). An assay to identify SCID and other T-cell deficiencies through quantification of T-cell recombinant excision circles (TRECs) has already been developed and is currently being used in pilot studies in Wisconsin and Massachusetts. In those two states, nearly 200,000 newborns have been screened without a SCID baby having been found, but other T-cell immunodeficiencies were identified in the screening. Because the TREC assay utilizes DNA technology, those laboratories with little experience, equipment or personnel in molecular biology may face challenges not encountered with an immunoassay. There exists a need for an alternative test for identifying alternate T-cell immunodeficiencies as well as alternate diagnostic kits.
SCID may result from a severe defect in both the T & B lymphocyte systems that leads to their diminishing. The absence of T-cells may be a defining characteristic of SCID and of other T-cell immunodeficiencies. (Edgar, J Clin Pathol 2008; 61:988-93). Because CD3 is part of the T-cell receptor complex on mature T-cells, it can be used as a marker for deficiency of T-cells (Dava, Immunol Rev. 2009; 232:22-33). Two case reports of CD3 deficiency causing immunodeficiency have been reported (Roberts et al., Blood 2007; 109:3198-3206, Rieux-Laucat et al., N Engl J. Med. 206; 354:1913-21). CD45, a common antigen present on all differentiated lymphocytes, provides an internal control for the assay. (Eley, Curr Allergy and Clin Immunol. March 2008:21:1-24).
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.